The National Cancer Institute, Cancer and Inflammation Program seeks parties interested in collaborative research to further co-develop inhibitors of STAT proteins for the treatment of cancer.
Signal transducer and activator transcription (STAT) proteins, specifically STAT1, 2, 3, 4, 5a, 5b, and 6, are involved in the cellular and biological processes of cell proliferation, differentiation, apoptosis, host defense, and transformation. Constitutively active STAT proteins occur in many human tumor cells and cells transformed by oncoproteins. Inhibiting these STAT proteins has great therapeutic potential in the treatment of certain cancers and a common approach to inhibition of these proteins involves targeting the kinases that activate STAT. This method typically leads to non-selective inhibitors and is associated with off-target related toxicity.
NCI scientists discovered a family of short peptides that bind to the N-terminal domains of STAT proteins and have shown that they can be used as therapeutic agents for certain types of cancer. These compounds are the first inhibitors that can directly bind to N-domains of STATs and exhibit a direct inhibitory effect. The selective nature of this direct approach suggests a more favorable toxicity profile than observed through the non-selective inhibition of kinases. STAT1, 3, and 5 inhibitors can serve as potent therapeutic agents for the treatment of a variety of tumors and STAT 4 inhibitors can be used to control autoimmune disorders.
- Therapeutic potential for the treatment of various cancer types, particularly for breast and prostate tumors.
- Potential use in the management of autoimmune disorders.
- As a research tool to study the function of STAT proteins
- The common method of down-regulation of STAT proteins
- Direct inhibition of STAT is associated with a reduced toxicity profile compared to down-regulation through inhibition of related kinases
Nadya I. Tarasova (NCI)
Timofeeva, OA, et al., STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain. PNAS. 110(4): 1267-1272, 2013. [PMID: 23288901]
- U.S. Patent Filed: U.S. Patent Application Number 12/601,711, Filed 05 Feb 2010